Advances in Stem Cell Research

Medical research involving the use of stem cells[1] has prompted
ethical and political debates among scientists, policymakers and the public. The most contentious aspect of the issue involves the retrieval of stem cells from human embryos, which are destroyed in the process. Legislation pending in
Michigan would, if enacted, allow exceptions to the state's longstanding ban on
the use of embryos for research.[2] This is an opportune time, then, to examine the science of stem cells.

Stem cells differ from other cells in the body in three
fundamental ways: they are capable of regenerating for a year or more; they do
not have a specialized function (as does a nerve cell or blood cell, for
example); and they generate specialized cells.[3]

Stem cells also are distinguished by their source. "Embryonic
stem cells" are derived from a "blastocyst," an embryo that is between five days and 10 days old and which consists of 100-150 cells that have developed
following fertilization. Embryonic stem cells can generate a variety of
specialized cell types throughout the body.

In contrast, "adult stem cells" start to emerge three to five
days after a blastocyst is formed. They, too, generate specialized cells that
maintain and repair tissue and organs. However, questions remain about the
extent to which adult stem cells are capable of generating specialized cells
other than those of the tissue from which they originate.[4]

Driving a good deal of research is the supposition that stem
cells can be "programmed" to grow healthy cells and tissue with which to treat a variety of injuries and diseases, such as spinal cord injury, stroke, burns,
heart disease, diabetes and rheumatoid arthritis. The ability to generate scores of identical stem cells could prove valuable in drug testing, too.

There also is hope that stem cell therapies may some day
alleviate the chronic shortage of donated organs. However, expectations are
tempered by the fact that the supply of human eggs from which to create embryos
for stem cell retrieval is limited.[5]

Some progress in stem cell therapy has been achieved: adult stem cells collected from bone marrow are being used to generate healthy blood cells to replace those destroyed by leukemia, Hodgkin's disease and anemia, for
example.[6] But a full complement of stem cell therapies has yet to be realized.

A primary obstacle to broader therapeutic applications is a lack of knowledge about the mechanisms that cause stem cells to develop into
specialized cells. It has been established that cell specialization[7] results from the activation of particular genes within a cell. What triggers a specific
genetic arrangement is not entirely known. The protein Oct-4 may play a role.[8]
But without a full understanding of this process, researchers are limited in
their ability to manipulate human stem cells to become the specialized cells
that can repair specific tissues or organs.

In experiments with mice, researchers have created specialized
cells from embryonic stem cells. However, the subsequent transplant of the
specialized cells produced tumors caused by unchecked cell growth. The
transplants also triggered rejection by the mice's immune systems.[9]

Embryonic stem cell research dates back two decades, when stem
cells were first isolated in the embryos of mice. In 1998, a research team led
by James Thomson at the University of Wisconsin isolated the first human
embryonic stem cells.

The principle source of embryonic stem cells has been embryos
created by in vitro fertilization[10] but not implanted in a woman's uterus.
According to a study by the Rand Corp., nearly 400,000 embryos have been frozen
and stored by fertility clinics since the late 1970s.[11] However, less than 3
percent of the embryos have been designated for research; the vast majority has
been stored for future implantation, according to the Rand study. This limited
supply, coupled with ethical concerns surrounding the destruction of the
embryos, has prompted researchers to look for alternative stem cell sources. As
a result, considerable attention is now focused on cloning.[12]

Cloning involves replacing the DNA of an unfertilized egg with
DNA retrieved from a cell in the patient's body. The result would be an embryo
from which stem cells could be generated. Because the resulting cells and tissue would carry the exact genetic makeup of the patient, the potential for
immunologic rejection would be virtually eliminated.

Scientists have succeeded in cloning embryonic stem cells from
mice, but a human egg has never been cloned. Some states ban human cloning, but
attempts elsewhere are underway. For example, Harvard University and the
University of California have inaugurated research programs to do so.[13]

Meanwhile, American and Japanese scientists recently announced a
remarkable breakthrough in stem cell research that may obviate the need for
embryos altogether. On Nov. 20, 2007,[14] two research teams – one led by Kyoto
University professor Shinya Yamanaka and the other led by James Thomson of the
University of Wisconsin – simultaneously and independently announced that they
had created stem cells that are "nearly indistinguishable" from human embryonic
stem cells without using either human eggs or human embryos.[15]

According to news accounts, the feat was accomplished by
injecting a cocktail of four proteins into the nucleus of skin cells. The Kyoto
team reported that they were able to grow brain and heart tissue from the
lab-created stem cells. The Wisconsin scientists created eight new stem cell
"lines"[16] for use in research.[17] However, both teams have warned that the procedure is far from perfected. Years of further testing must still be undertaken to ensure safety.

Currently, federal funding of embryonic stem cell research is
restricted to lines created before Aug. 9, 2001. The embryos from which these
lines originated had to have been created for reproductive purposes and
subsequently classified as "medical waste." Donor consent – without financial
inducement – also was required.[18] There were 71 embryos among 14 laboratories
worldwide[19] that were generating stem cell lines in 2001.[20]

There is disagreement about whether existing lines of embryonic
stem cells are sufficient for ongoing research. In June 2007, President George
Bush authorized federal funding of research involving stem cells derived from
sources other than embryos, such as amniotic fluid, umbilical cords and skin
cells.

Despite the restrictions on federal funding, research on
embryonic and adult stem cells continues in many laboratories across the nation,
supported by both private and public funds. Ten states currently fund embryonic
stem cell research.

Michigan's prohibition on the use of embryos for experimentation
was enacted in 1978. Cloning is likewise banned. But state law does permit the
use of embryonic stem cells in research within Michigan labs as long as they
have been retrieved from embryos outside of the state.

House Bill 4616 would, if enacted, allow the retrieval of stem
cells from embryos in the state if the embryos are classified as medical waste,
i.e., not intended for implantation. The bill also would allow families to
donate unused embryos for research. The legislation is tie-barred[23] to HB 4617 and HB 4618, which propose to increase the penalties for human cloning from 10 years in prison to 15 years in prison and a maximum fine of $10 million, while also raising such a violation from a Class D felony to a Class C offense.

As debate continues over stem cell research, scientific advances
are occurring at a relatively rapid pace. The prospects have greatly improved
for creating embryonic-type stem cells without destroying embryos. Thus, it may
well be that science will solve the political and ethical dilemmas long before
the politicians do.

[1] Stem cells are the most rudimentary type of cell. They are capable of replicating for as long as a year, and they generate the specialized cells from which tissue and organs grow.

[10] A technique that unites the egg and sperm in a laboratory, instead of inside the female body.

[11] Hoffman DI, Zellman GL, Fair CC, Mayer JF, Zeitz, JG, Gibbons WE and Turner TG., "Cryopreserved Embryos in the United States and Their Availability for Research," Fertility and Sterility 79 (5): 1063-1069. For more information go to www.rand.org/pubs/research_briefs/RB9038/RB9038.pdf.

[12] The technical term for the procedure is somatic cell nuclear transfer.